Is PGAP2 p.Met267Val (c.799A>G) pathogenic?

PGAP2 p.Met267Val (c.799A>G) is classified Uncertain significance in PGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.00667%, amr).

How common is PGAP2 p.Met267Val (c.799A>G) in the general population?

PGAP2 p.Met267Val (c.799A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about PGAP2 p.Met267Val (c.799A>G)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

PGAP2 p.Met267Val

c.799A>G · rs1173487235 · VCV1917621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.023 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M206V vs ClinVar M267V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,014 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000434% 7/1,614,050 alleles · very rare exomes 7/1,461,848 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,004
European (non-Finnish)	0.000254%	393,324

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PGAP2
Protein: p.Met267Val
Coding: c.799A>G
MANE Select: NM_014489
dbSNP: rs1173487235
Type: single nucleotide variant
Location: chr11:3825110 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00

Full PGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PGAP2 p.Ala127Val Likely pathogenic ★★ same type
PGAP2 p.Arg238Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
PGAP2 p.Thr294Met Likely pathogenic ★★ same type
PGAP2 c.602-3C>T Uncertain significance ★★ same type
PGAP2 p.Ala187Thr Uncertain significance ★★ ⚠ same type
PGAP2 p.Ala33Thr Uncertain significance ★★ ⚠ same type
PGAP2 p.Arg238Cys Uncertain significance ★★ ⚠ same type
PGAP2 p.Asn205Lys Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pgap2-p-met267val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown